Lafutidine-induced increase in intracellular ca(2+) concentrations in PC12 and endothelial cells.
Lafutidine-induced increase in intracellular ca(2+) concentrations in PC12 and endothelial cells.
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DOI：
10.1254/jphs.fpj04042x
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发表时间：
2005
影响因子：
3.5
通讯作者：
K. Kunieda;Akiyoshi Someya;S. Horie;H. Ajioka;T. Murayama
中科院分区：
文献类型：
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作者：
K. Kunieda;Akiyoshi Someya;S. Horie;H. Ajioka;T. Murayama
Lafutidine 是一种组胺 H(2) 受体拮抗剂，除了具有胃抗分泌活性外，还具有胃保护作用。拉呋替丁的胃肠道保护作用是由辣椒素敏感神经元介导的，其中辣椒素通过打开瞬时受体电位通道家族（TRPV1）的成员来兴奋神经元。由于拉呋替丁对细胞内Ca(2+)浓度([Ca(2+)](i))的影响尚未阐明，我们研究了拉呋替丁对大鼠嗜铬细胞瘤PC12和人内皮细胞中[Ca(2+)](i)的反应。在 PC12 细胞中存在细胞外 CaCl(2) 的情况下，药理学浓度大于 1 mM 的拉呋替丁可诱导 [Ca(2+)](i) 持续增加，而辣椒素对 PC12 细胞中的 [Ca(2+)](i) 显示出双重作用，它激活 TRPV1 并抑制钙池操纵的 Ca(2+) 进入。辣椒素和 SKF96365（一种钙池操纵的 Ca(2+) 进入激活剂）诱导的 PC12 细胞中 [Ca(2+)](i) 增加被辣椒素和 SKF96365（一种钙池操纵的 Ca(2+) 进入抑制剂）抑制，并且拉呋替丁反应被辣椒素抑制，但不被 SKF96365 抑制。在内皮细胞中，拉呋替丁以 SKF96365 不敏感的方式诱导 [Ca(2+)](i) 增加。这些结果表明，拉呋替丁通过辣椒素敏感途径刺激 Ca(2+) 进入，但不通过 SKF96365 敏感途径刺激 Ca(2+) 进入。还讨论了拉呋替丁诱导的钙池操纵的 Ca(2+) 内流对胃肠功能的可能作用。
Lafutidine, a histamine H(2) receptor antagonist, exerts gastroprotective effects in addition to gastric antisecretory activity. The gastrointestinal protective effects of lafutidine are mediated by capsaicin-sensitive neurons, where capsaicin excites neurons by opening a member of the transient receptor potential channel family (TRPV1). Since the effect of lafutidine on the intracellular Ca(2+) concentration ([Ca(2+)](i)) in cells has not been elucidated, we investigated the lafutidine response to [Ca(2+)](i) in rat pheochromocytoma PC12 and human endothelial cells. Lafutidine at pharmacological concentrations greater than 1 mM induced a sustained increase in [Ca(2+)](i) in the presence of extracellular CaCl(2) in PC12 cells, while capsaicin showed dual effects on [Ca(2+)](i) in PC12 cells, where it activated TRPV1 and inhibited store-operated Ca(2+) entry. The thapsigargin (an activator of store-operated Ca(2+) entry)-induced increase in [Ca(2+)](i) in PC12 cells was inhibited by capsaicin and SKF96365, an inhibitor of store-operated Ca(2+) entry, and the lafutidine response was inhibited by capsaicin but not by SKF96365. In endothelial cells, lafutidine induced an increase in [Ca(2+)](i) in a SKF96365-insensitive manner. These results suggest that lafutidine stimulates Ca(2+) entry via the capsaicin-sensitive pathway but not the SKF96365-sensitive pathway. The possible role of store-operated Ca(2+) entry induced by lafutidine on gastrointestinal function is also discussed.